palonosetron
Brand: Aloxi
Prototype: ondansetron
Drug Class: 5-HT3 receptor antagonist
Drug Family: antiemetic
Subclass: second-generation long-acting 5-HT3 antagonist
Organ Systems: gastrointestinal
Mechanism of Action
Selectively antagonizes 5-HT3 receptors with 100-fold higher binding affinity than first-generation agents; also exhibits allosteric binding causing receptor internalization, which contributes to its prolonged antiemetic effect.
5-HT3 receptors
Indications
- acute and delayed CINV (highly emetogenic chemotherapy)
- PONV (prevention)
Contraindications
- hypersensitivity to palonosetron
Adverse Effects
Common
- headache
- constipation
- dizziness
Serious
- QT prolongation (less than first-generation agents)
- serotonin syndrome
Pharmacokinetics (ADME)
| Absorption | IV administration (standard formulation); oral capsule available |
| Distribution | 62% protein bound |
| Metabolism | 50% metabolized hepatically; 50% excreted unchanged |
| Excretion | renal (~80%) |
| Half-life | 40 hours |
| Onset | 30 minutes |
| Peak | end of infusion |
| Duration | up to 5 days |
| Protein Binding | 62% |
| Vd | 8.3 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| QT-prolonging agents | additive QT prolongation (lower risk than first-generation) | moderate |
| serotonergic drugs | serotonin syndrome risk | major |
Nursing Considerations
- Administer IV palonosetron 30 minutes before chemotherapy as a single dose; single IV dose is effective for both acute and delayed CINV.
- Unlike ondansetron, a single dose provides up to 5 days of antiemetic coverage, avoiding the need for additional antiemetic doses.
- Monitor for constipation as a common adverse effect, particularly in oncology patients on opioids.
- Assess for drug interactions with other serotonergic drugs to prevent serotonin syndrome.
Clinical Pearls
- Palonosetron is the preferred 5-HT3 antagonist for highly emetogenic chemotherapy regimens because its 40-hour half-life covers both acute (0–24 h) and delayed (24–120 h) CINV phases.
- Unlike ondansetron, palonosetron uniquely allosterically modulates the 5-HT3 receptor, causing receptor internalization and contributing to its prolonged action.
Safety Profile
Pregnancy generally-safe
Lactation use-with-caution
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.